This information is intended for use by health professionals

1. Name of the medicinal product

Loratadine 10 mg Orodispersible Tablets

Boots Hayfever Relief Instant-Melts 10 mg Orodispersible Tablets

2. Qualitative and quantitative composition

Each orodispersible tablet contains 10 mg loratadine.

Excipients with known effect

Each orodispersible tablet contains 0.5 mg aspartame (E 951), 15 mg lactose anhydrous and not more than 7 mg sorbitol (E 420).

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Orodispersible tablet.

White, round, flat tablet.

4. Clinical particulars
4.1 Therapeutic indications

Loratadine 10mg Orodispersible Tablet is indicated for the symptomatic treatment of allergic rhinitis (AR) and chronic idiopathic urticaria (CIU).

4.2 Posology and method of administration

Posology

Adults and children over 12 years of age

10 mg once daily (one orodispersible tablet once daily).

Paediatric population

Children 2 to 12 years of age with body weight more than 30 kg: 10 mg once daily (one orodispersible tablet once daily).

The 10 mg strength orodispersible tablet is not appropriate in children with a body weight less than 30 kg.

Efficacy and safety of loratadine in children under 2 years of age has not been established.

Hepatic impairment

Patients with severe hepatic impairment should be administered a lower initial dose because they may have reduced clearance of loratadine. An initial dose of 10 mg every other day is recommended for adults and children weighing more than 30 kg.

Renal impairment

No dose adjustments are required in patients with renal insufficiency.

Elderly

No dosage adjustments are required in the elderly.

Method of administration

Loratadine 10 mg orodispersible tablets should be handled with caution and with dry hands only.

Loratadine 10 mg orodispersible tablets are intended for oral use.

The tablet shall be put on the tongue and wait until it is thoroughly disintegrated. Water or other liquid is not needed to swallow the dose.

The orodispersible tablet may be taken without regard to mealtime.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Loratadine should be administered with caution in patients with severe hepatic impairment (see section 4.2).

This product contains lactose and sorbitol. Patients with rare hereditary problems of fructose intolerance, galactose intolerance, the total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

This product contains aspartame. Aspartame is a source of phenylalanine, which may be harmful for people with phenylketonuria.

This medicine contains less than 1 mmol (23 mg) sodium per orodispersable tablet, that is to say essentially 'sodium-free'.

The administration of loratadine should be discontinued at least 48 hours before skin tests since antihistamines may prevent or reduce otherwise positive reactions to dermal reactivity index.

4.5 Interaction with other medicinal products and other forms of interaction

When administered concomitantly with alcohol, loratadine has no potentiating effects as measured by psychomotor performance studies.

Potential interaction may occur with all known inhibitors of CYP3A4 or CYP2D6 resulting in elevated levels of loratadine (see section 5.2), which may cause an increase in adverse events.

Increase in plasma concentrations of loratadine has been reported after concomitant use with ketoconazole, erythromycin, and cimetidine in controlled studies, but without clinically significant changes (including electrocardiographic).

Paediatric population

Interaction studies have only been performed in adults.

4.6 Fertility, pregnancy and lactation

Pregnancy

A large amount of data on pregnant women (more than 1000 exposed outcomes) indicate no malformative nor feto/ neonatal toxicity of loratadine.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of loratadine during pregnancy.

Breast-feeding

Loratadine is excreted in breast milk, therefore the use of loratadine is not recommended in breastfeeding women.

Fertility

There are no data available on male and female fertility.

4.7 Effects on ability to drive and use machines

In clinical studies that assessed driving ability, no impairment occurred in patients receiving loratadine. Loratidine has no or negligible influence on the ability to drive and use machines. However, patients should be informed that very rarely some people experience drowsiness, which may affect their ability to drive or use machines.

4.8 Undesirable effects

Summary of the safety profile

In clinical studies involving adults and adolescents in a range of indications including allergic rhinitis (AR) and chronic idiopathic urticaria (CIU), at the recommended dose of 10 mg daily, adverse reactions with loratadine were reported in 2% of patients in excess of those treated with placebo. The most frequent adverse reactions reported in excess of placebo were somnolence (1.2%), headache (0.6%), increased appetite (0.5%) and insomnia (0.1%).

List of adverse reactions

The following adverse reactions reported during the post-marketing period are listed in the following table by System Organ Class. Frequencies are defined as:

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

System Organ Class

Frequency

Adverse reaction

Immune system disorders

Very rare

Hypersensitivity reactions (including angioedema and anaphylaxis)

Nervous system disorders

Very rare

Dizziness, convulsion

Cardiac disorders

Very rare

Tachycardia, palpitation

Gastrointestinal disorders

Very rare

Nausea, dry mouth, gastritis

Hepatobiliary disorders

Very rare

Abnormal hepatic function

Skin and subcutaneous tissue disorders

Very rare

Rash, alopecia

General disorders and administration site conditions

Very rare

Fatigue

Investigations

Not known

Weight increased

Paediatric population

In clinical studies in a paediatric population, children aged 2 through 12 years, common adverse reactions reported in excess of placebo were headache (2.7%), nervousness (2.3%), and fatigue (1%).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Overdose with loratadine increased the occurrence of anticholinergic symptoms. Somnolence, tachycardia, and headache have been reported with overdoses.

In the event of overdose, general symptomatic and supportive measures are to be instituted and maintained for as long as necessary. Administration of activated charcoal as a slurry with water may be attempted. Gastric lavage may be considered. Loratadine is not removed by haemodialysis and it is not known if loratadine is removed by peritoneal dialysis. Medical monitoring of the patient is to be continued after emergency treatment.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: antihistamines – H1 antagonist, ATC code: R06A X13.

Mechanism of action

Loratadine, the active substance in the medicinal product, is a tricyclic antihistamine with selective, peripheral Hl-receptor activity.

Pharmacodynamic effects

Loratadine has no clinically significant sedative or anticholinergic properties in the majority of the population and when used at the recommended dose.

During long-term treatment there were no clinically significant changes in vital signs, laboratory test values, physical examinations or electrocardiograms.

Loratadine has no significant H2-receptor activity. It does not inhibit norepinephrine uptake and has practically no influence on cardiovascular function or on intrinsic cardiac pacemaker activity.

Human histamine skin wheal studies following a single 10 mg dose has shown that the antihistamine effects are seen within 1-3 hours, reaching a peak at 8-12 hours and lasting in excess of 24 hours. There was no evidence of tolerance to this effect after 28 days of dosing with loratadine.

Clinical efficacy and safety

Over 10,000 subjects (12 years and older) have been treated with loratadine 10 mg tablets in controlled clinical studies. Loratadine 10 mg tablets once daily was superior to placebo and similar to clemastine in improving the effects on nasal and non-nasal symptoms of AR. In these studies somnolence occurred less frequently with loratadine than with clemastine and about the same frequency as terfenadine and placebo.

Among these subjects (12 years and older), 1000 subjects with CIU were enrolled in placebo controlled studies. A once daily 10 mg dose of loratadine was superior to placebo in the management of CIU as demonstrated by the reduction of associated itching, erythema and hives. In these studies the incidence of somnolence with loratadine was similar to placebo.

Paediatric population

Approximately 200 paediatric subjects (6 to 12 years of age) with seasonal allergic rhinitis received doses of loratadine syrup up to 10 mg once daily in controlled clinical studies. In another study, 60 paediatric subjects (2 to 5 years of age) received 5 mg of loratadine syrup once daily. No unexpected adverse events were observed.

The paediatric efficacy was similar to the efficacy observed in adults.

5.2 Pharmacokinetic properties

Absorption

Loratadine is rapidly and well absorbed. Concomitant ingestion of food can delay slightly the absorption of loratadine but without influencing the clinical effect.

Distribution

Loratadine is highly bound (97 % to 99 %) and its active metabolite desloratadine (DL) moderately bound (73 % to 76 %) to plasma proteins.

In healthy subjects, plasma distribution half-lives of loratadine and its active metabolite are approximately 1 and 2 hours, respectively.

Biotransformation

After oral administration, loratadine is rapidly and well absorbed and undergoes an extensive first pass metabolism, mainly by CYP3A4 and CYP2D6. The major metabolite -desloratadine (DL)- is pharmacologically active and responsible for a large part of the clinical effect. Loratadine and DL achieve maximum plasma concentrations (tmax) between 1-1.5 hours and 1.5-3.7 hours after administration, respectively.

Elimination

The mean elimination half-lives in healthy adult subjects were 8.4 hours (range = 3 to 20 hours) for loratadine and 28 hours (range = 8.8 to 92 hours) for the major active metabolite.

Approximately 40 % of the dose is excreted in the urine and 42 % in the faeces over a 10 day period and mainly in the form of conjugated metabolites. Approximately 27 % of the dose is eliminated in the urine during the first 24 hours. Less than 1 % of the active substance is excreted unchanged in active form, as loratadine or DL.

Linearity

The bioavailability parameters of loratadine and of the active metabolite are dose proportional.

Elderly

The pharmacokinetic profile of loratadine and its metabolites is comparable in healthy adult volunteers and in healthy geriatric volunteers.

Renal impairment

In patients with chronic renal impairment, both the AUC and peak plasma levels (Cmax) increased for loratadine and its active metabolite as compared to the AUCs and peak plasma levels (Cmax) of patients with normal renal function. The mean elimination half-lives of loratadine and its active metabolite were not significantly different from that observed in normal subjects. Haemodialysis does not have an effect on the pharmacokinetics of loratadine or its active metabolite in subjects with chronic renal impairment.

Hepatic impairment

In patients with chronic alcoholic liver disease, the AUC and peak plasma levels (Cmax) of loratadine were double while the pharmacokinetic profile of the active metabolite was not significantly changed from that in patients with normal liver function. The elimination half-lives for loratadine and its metabolite were 24 hours and 37 hours, respectively, and increased with increasing severity of liver disease.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard based on conventional studies of safety, pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.

In reproductive toxicity studies, no teratogenic effects were observed. However, prolonged parturition and reduced viability of offspring were observed in rats at plasma levels (AUC) 10 times higher than those achieved with clinical doses.

No evidence of mucous membrane irritation was observed after daily administration of up to 12 tablets (120 mg) of oral lyophilisates into the hamster cheek pouch for five days.

6. Pharmaceutical particulars
6.1 List of excipients

Sweet orange flavour

Aspartame (E 951)

Citric acid anhydrous (E 330)

Silica, colloidal anhydrous (E 551)

Maize starch, dried

Lactose anhydrous

Magnesium stearate (E 470b)

Croscarmellose sodium (E 468)

Mannitol (E 421)

Sorbitol (E 420)

Crospovidone

Silica, colloidal hydrated (E 551)

Polysorbate 80 (E 433)

Povidone (E 1201)

Microcrystalline cellulose (E 460)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store in the original package in order to protect from moisture.

6.5 Nature and contents of container

Unit dose perforated blisters (Alu/Alu).

Packs of 7x1, 14, 21x1, 30x1 orodispersible tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. Marketing authorisation holder

Sandoz Ltd

Frimley Business Park

Frimley

Camberley

Surrey

GU16 7SR

8. Marketing authorisation number(s)

PL 04416/0693

9. Date of first authorisation/renewal of the authorisation

06/02/2007

10. Date of revision of the text

22/09/2018